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Effects on median nerve SEPs of tactile stimulation applied to adjacent and remote areas of the body surface
252
Electroencephalograph), and clinical Neurophysiologr', 1985, 62:252-265
Elsevier Scientific Publishers Ireland, Ltd.
EFFECTS ON MEDIAN NERVE SEPs OF TACTILE AND REMOTE AREAS OF THE BODY SURFACE
STIMULATION
APPLIED
TO
ADJACENT
RYUSUKE KAK1GI 1 and S.J. JONES Medical Research Council, National Hospital for Nervous Diseases, Queen Square, London W C I N 3BG ( U.K.)
(Accepted for publication: January 26, 1985)
Summary Study of the influence of continuous tactile stimulation on somatosensory evoked potentials (SEPs) following electrical stimulation of the median nerve revealed an effect due to interfering input from both adjacent and remote regions of the body surface. The distribution of the effect was demonstrated by subtracting the 'interference' from the 'control' response to derive a 'difference' wave form. Tactile stimulation of the thumb ipsilateral to the stimulated median nerve produced a difference wave form in which a marked phase reversal was apparent between pre- and post-central areas for 2 complexes, at latencies of approximately 20 and 30 msec. It is proposed that this may have been due to partial 'saturation' of a generator in the hand region of area 3b in the primary somatosensory cortex (SI), which was then unable to respond fully to the median nerve impulse. A similar effect was observed when the interfering stimulus was applied to the ipsilateral little finger, possibly reflecting a process of 'surround inhibition.' Tactile stimulation of more remote regions (principally the face and contralateral hand) resulted in consistent difference wave forms in which the early components (less than 30 msec latency) had scalp distributions differing from one another but consistent with influence on generators in the face or hand region of the second somatosensory cortex (SII). Later potentials consistently identifiable in the difference wave forms were similar for all locations of the interfering stimulus apart from the ipsilateral thumb and were distributed in accordance with a proposed generator in the parietal 'association' cortex. Keywords: somatosenso O' evoked potentials ( S E P s ) - - electrical and mechanical stimulation
tactile interference - -
mechanorecep-
tors - - S I and S I I cortical areas - - parietal association cortex
O n e of the m a j o r p r o b l e m s in the i n t e r p r e t a t i o n of conventional somatosensory evoked potentials ( S E P s ) f o l l o w i n g electrical s t i m u l a t i o n of the m e d i a n n e r v e at t h e wrist is t h a t fibers s e r v i n g m o r e t h a n o n e s e n s o r y m o d a l i t y a n d p r o j e c t i n g to d i f f e r e n t a r e a s o f c o r t e x are s t i m u l a t e d s i m u l t a n e o u s l y . R e c e n t a d v a n c e s in m i c r o n e u r o g r a p h y h a v e d e m o n s t r a t e d that the h u m a n m e d i a n n e r v e c o n t a i n s large d i a m e t e r a f f e r e n t fibers of m a n y types, r e s p o n d i n g to s t i m u l i such as d e f o r m a t i o n o f the skin, p a s s i v e m u s c l e stretch, v o l u n t a r y c o n t r a c t i o n , d e e p p r e s s u r e o r v i b r a t i o n (see V a l l b o et al. 1979). T h e p r i m a r y s o m a t o s e n s o r y c o r t e x (SI) is n o w k n o w n to c o n t a i n at least 4 r e p r e s e n t a t i o n s o f the b o d y , c o r r e s p o n d i n g to areas 1, 2, 3a a n d 3b, e a c h o f w h i c h a p p e a r s to b e a s s o c i a t e d w i t h s e n s o r y i n p u t of a p a r t i c u l a r m o d a l i t y o r c o m b i n a Ryusuke Kakigi was supported by a Research Fellowship from the Wellcome Trust in the United Kingdom.
t i o n o f m o d a l i t i e s (see K a a s et al. 1981). In a d d i t i o n , the s e c o n d a r y s o m a t o s e n s o r y c o r t e x (SIt), w h i c h in m o n k e y s is s i t u a t e d o n the s u p e r i o r b a n k o f the sylvian fissure, is k n o w n to c o n t a i n units w h i c h are a c t i v a t e d by light t o u c h a p p l i e d to the skin o f the ipsilateral, as well as the c o n t r a l a t e r a l b o d y s u r f a c e ( M a r k a n d S t e i n e r 1958; C a r r e r a s a n d A n d e r s s o n 1963; W h i t s e l et al. 1969; R o b i n son 1973). T w o d i f f e r e n t m e t h o d s h a v e b e e n a d o p t e d in o r d e r to try to i d e n t i f y S E P c o m p o n e n t s specifically a s s o c i a t e d w i t h the p r o c e s s i n g o f i n p u t f r o m c u t a n e o u s m e c h a n o r e c e p t o r s . O n e is to s t u d y p o t e n t i a l s e v o k e d b y m e c h a n i c a l s t i m u l a t i o n of the b o d y s u r f a c e (see K a k i g i a n d S h i b a s a k i 1984). A n a l t e r n a t i v e a p p r o a c h is to see h o w e l e c t r i c a l l y e v o k e d S E P s are a f f e c t e d by c o n t i n u o u s ' i n t e r f e r i n g ' tactile stimuli a p p l i e d to the skin ( G i b l i n 1964; J o n e s 1981; J o n e s a n d P o w e r 1984). In a p r e v i o u s s t u d y ( J o n e s a n d P o w e r 1984) the
0168-5597/85/$03.30 © 1985 Elsevier Scientific Publishers Ireland, Ltd.
A D J A C E N T A N D R E M O T E I N T E R F E R E N C E EFFECTS ON SEPs
253
electrical stimulus was delivered to the median nerve and the interfering stimulus to the ipsilateral palm. By subtracting the 'interference' wave form so obtained from a 'control' wave form, a 'difference' wave form was derived in which the 2 major components were a positivity, maximal over the contralateral parietal cortex, and a negativity of similar latency and duration with a fairly symmetrical distribution in frontal regions. It was proposed that these might be attributable to a single generator situated in the posterior bank of the central sulcus, corresponding to area 3b. In an earlier study (Jones 1981) there was a suggestion that SEPs might also be influenced by light touch stimulation of other parts of the body. The object of the present investigation, therefore, was to examine changes in the wave form of conventional electrically evoked SEPs, produced by continuous tactile stimulation of various parts of the body such as the face, hand, forearm and foot ipsilateral and contralateral to the stimulated median nerve.
Material and Methods Fourteen normal volunteers, 10 men and 4 women, were studied. Their ages ranged from 19 to 35 years with a mean age of 31. Their height ranged from 152 to 184 cm (mean 168). Recordings were performed in a quiet room. The subject was sealed comfortably in a reclining arm-chair and was encouraged to relax. No medication was given and the subject was kept awake. The electrical stimulus was a constant voltage square-wave impulse delivered to the right median nerve at the wrist. The stimulus duration was 0.2 msec, the intensity sufficient to produce a definite twitch of the thumb and the frequency 5/sec. In the initial study of 12 subjects, 8 recording electrodes were attached to the scalp at locations Fpz, F3, C3, Cz, C4, P3, O1 and 0 2 of the 10-20 system. A separate and more detailed topographical study was made in 7 subjects with 16 electrodes located over the scalp contralateral to the stimulus, at F7, F3, T3, C5, C3, C1, T5, P3 and additional locations 1-8 as shown in Fig. 1. Location 1 was just anterior to the tragus and
Fig. 1. Electrode placements used for the 8- and 16-channel montages. Location 1 was ~ust anterior to the tragus, location 5 on the mastoid process and the reference on the right earlobe (A2).
location 5 at the mastoid process. All sites were referred to A2 (right earlobe). The high-frequency response of the amplifier was less than 3 dB down at 5 kHz and the time constant was 1 sec. The average of 1000 responses was computed, on 8 or 16 channels simultaneously, using a digital averager with an epoch of 85 msec starting 3 msec after the stimulus and a sampling interval of 0.33 msec. Continuous light tactile stimulation was delivered by the experimenter concurrently with the median nerve stimulus, using a soft wad of tissue paper or a manually rotated cylinder (diameter 4 cm) covered in wool carpeting. Tissue paper was used to stimulate the pad of the thumb and little finger, the forearm, face (perioral areas and lips)
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R. KAKIGI, S.J. JONES
and the sole of the foot ipsilateral to the stimulated median nerve, and the face, forearm and foot on the contralateral side. The contralateral palm was stimulated by means of the cylinder, loosely resting in contact with the thumb and the 2nd and 3rd digits and rotated at 1 - 2 rev/sec. In the initial series of 12 subjects, using the 8-channel montage, 2 or 3 average responses were recorded of the 'control' SEP (without tactile interference) and of 'interference' SEPs with continuous tactile stimulation of each skin area ipsilateral to the median nerve stimulus, and the contralateral palm. The remaining contralateral regions were stimulated ill 8 subjects. In the second series of 7 subjects, for whom the 16-channel montage was employed, 4 average responses were recorded of the 'control' SEP and of 'interference' SEPs with continuous tactile stimulation of the ipsilateral little finger, the ipsilateral face and the contralateral palm. The order of the 'control' and 'interference' conditions was alternated to control for long-term trends throughout the recording session. Grand average wave forms were computed for each stimulus condition in each subject and then combined in group average wave forms. Isopotential maps were plotted from the 16channel group average difference wave forms, at intervals of 1 msec between 14 and 78 msec following the stimulus. Peak latencies and peak-to-peak amplitudes were measured for consistently identifiable components.
attenuated or enhanced under the interference condition. The overall trend was best demonstrated by subtracting the 'interference' from the 'control' wave form, but the peaks seen in the 'difference' wave form did not correspond precisely in latency with potentials identified in the directly obtained wave forms. Consequently it was not possible to explain the difference peaks simply in terms of attenuation or enhancement of potentials in the conventional median nerve response. In the difference wave form the following components were identifiable ( ' U ' signifying an upward deflection and ' D ' downward, see Table l): U21 and D31 potentials at the P3 electrode spreading to O1, 0 2 and (D31 only) C3; U65 and D85 at C3 spreading to P3 and O1; D21, U34, D57 and U78 at F3, the last 3 spreading to Fpz. A small downward potential, DI4, was recognized at the Ol and 0 2 locations but was absent at more frontal electrodes. The U21 and D31 components recorded at P3 demonstrated an apparent phase reversal with D21 and U34 respectively at F3, although U34 was of slightly longer duration and peak latency than D31. U65 recorded at C3 and P3 overlapped in duration with D57 recorded at F3, the peak latencies differing by 8-10 msec. No significant difference potentials were present at Cz or C4 except for some spread of U34 at Cz. These effects were very similar to those produced by stimulating the whole of the palm (Jones and Power 1984), and so were not studied further using the 16-channel montage.
Results
(2) Ipsilateral little finger interference effect
(1) lpsilateral thumb interference effect The most consistent and reproducible interference effect amongst all conditions of the present study was obtained with tactile stimulation of the thumb ipsilateral to the electrically stimulated median nerve. Fig. 2 shows the group average 'control,' 'interference' and 'difference' wave forms obtained with the 8-channel montage from 12 subjects. Although clear differences can be seen between the control and interference conditions, apparently reflecting attenuation of some components and enhancement of others, it could not be stated categorically that the wave form was either
With continuous tactile stimulation of the little finger ipsilateral to the electrically stimulated median nerve, consistent differences were also present between the 'control' and 'interference' wave forms. As for the thumb interference effect, however, these appeared to consist of attenuation of some components and enhancement of others, and the overall effect was more clearly revealed in the 'difference' wave form (Fig. 3A and Table I). At F3 an ill-defined downward potential peaking at 23 msec was followed by consistent U32 and D59 components, similar to components present in the ipsilateral thumb difference wave form. At the P3 electrode an ill-defined upward deflection
ADJACENT AND REMOTE INTERFERENCE EFFECTS ON SEPs Ipsilateral
thumb
interference
Control .....
'"T"-T'T"-T'-T'T"'"T'"'""r'
255
effect
(average
Interference 'T""'T'T"'"'T'"'""r'"'""r'"'"'T'"""T
.....
TM
of
12
subjects)
Difference '""I'"""T'"'"'T'"'"'T'"'"'T'"""T'"'"'T'"'"'T'"'"' U34
Fpz F3
D21
D57
U65 C3
Cz C4
I IJ.V P3 01 02
......I.........I.........I.........I.........I.........I.........I.........I............... I.........I.........I.........I.........I.........I.........I.........I........ 10
30
50
70
ms
10
30
50
70
ms
.......I.........I.........I......... I.........I.........I......... I.........I........ 10 30 50 7 0 ms
Fig. 2. Group average wave forms (12 subjects) of the 'control' (without interference), 'interference" (with continuous tactile stimulation applied to the right thumb) and 'difference' (derived by subtraction of the 'interference' from the "control' wave form) SEPs, 8-channel montage. Stimulation of the fight median nerve at the wrist with the right earlobe (A2) as reference and negativity at grid 1 upward in this and all following figures. p e a k i n g at a p p r o x i m a t e l y 20 msec was followed by a consistent D31 s p r e a d i n g to O1 a n d 0 2 , a n d similar to D31 in the t h u m b difference wave form. D31 at P3, therefore, d e m o n s t r a t e d an a p p a r e n t p h a s e reversal with U32 at F3. T h e difference wave form at C3 consisted of a d o w n g o i n g p e a k (D26) which a p p e a r e d to be a c o m p o s i t e of p o t e n tials present at P3 a n d F3. F o l l o w i n g a return t o w a r d s the baseline a second d o w n w a r d p e a k (D54) was m a x i m a l at C3, s p r e a d i n g to P3 a n d O1. N o similar p o t e n t i a l was consistently identifiable in the t h u m b difference wave form. D54 was followed b y an u p w a r d p e a k (U68) with a similar d i s t r i b u t i o n , c o m p a r a b l e with U65 in the t h u m b difference wave form a l t h o u g h of m u c h smaller amplitude. T h e m a i n features of the ipsilateral little finger
difference wave form were c o n f i r m e d in 7 subjects using a m o n t a g e of 16 electrodes over the left hemisphere, referred to the right ear lobe (Fig. 4). A d d i t i o n a l l y , an initial u p w a r d p e a k (U20) and d o w n w a r d p e a k (D22) were m o r e clearly identifiable, the former w i d e s p r e a d over the p o s t e r i o r q u a d r a n t a n d the latter present at C1, C3 and i n t e r m e d i a t e location 4. As in the 8-channel d a t a U32 was m a x i m a l at F3, b u t was also p r e s e n t at a d j a c e n t sites ( i n t e r m e d i a t e location 4 a n d C1). D31 was again m a x i m a l at P3, s p r e a d i n g to all sites in the p o s t e r i o r q u a d r a n t a n d also to C5 a n d T3. A t C3 the early p a r t of the wave form was t r a n s i t i o n a l between that r e c o r d e d a n t e r i o r l y and posteriorly, b u t in this g r o u p of subjects no D26 p o t e n t i a l was a p p a r e n t . D54 was widely distribu t e d at central a n d parietal locations, with maxi-
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R. KAKIGI, S.J. JONES
TABLE I Peak latency and amplitude of each consistently recognizable component maximally recorded at the F3, C3 and P3 electrodes (8-channel montage) in the ipsilateral thumb, ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms, Electrode site
Potential
Number of subjects
Mean latency _+1 S.D. (msec)
Latency of group averagewave form (msec)
Mean amplitude _+1 S.D. (/*V)
F3
D21 U34 D57 U78
12/12 12/12 12/12 11/12
20.9 ± 1.9 32.8 ± 3.1 55.9 _+7.3 73.9 ± 6.4
21.0 33.6 57.3 78.0
0.5 ± 0.2 1.2 ± 0.3 1.4 _+0.7 1.1 ± 0.6
C3
U65 D85
9/12 7/12
66.2 _+6.0 79.9_+6.3
65.2 85.0
1.8 + 0.8 1.9 ± 0.8
P3
U21 D31
12/12 12/12
21.4 _+2.2 32.4 ± 3.1
20.5 31.1
0.4 ± 0.3 1.4 + 0.7
F3
U32 D59
12/12 12/12
32.5 _+3.1 58.8 _+5.0
31.9 59.1
0.8 + 0,5 1.3 + 0.7
C3
D26 D54 U68
11/12 12/12 12/12
26.1 ± 3.1 52.4_+4.6 68.8 ± 7.6
25.8 53.5 68.2
0.7 ± 0,5 1.2 ± 1,0 1.3 _+1.0
P3
D31
11/12
29.0 ± 3.6
30.8
1.0 ± 0.6
Ipsilateral face
C3
D27 U41 D52 U65
12/12 10/12 11/12 10/12
27.1 _+3.7 40.3 ± 5.1 52.8_+4.4 68.8 ± 6.4
27.0 40.6 51.3 64.4
0.8 ± 0.4 1.2 ± 0.6 1.1 _+0.5 1.2 + 0.9
Contralateral palm
F3
D27 U45 D69
11/12 11/12 11/12
28.2 _+2.9 45.1 ± 6.5 64.9 _+7.4
26.8 44.9 68.5
0.5 ± 0.4 0.8 _+0.4 1.1 ± 0.6
C3
D56
12/12
57.2 ± 7.1
55.7
1.3 ± 0.5
Ipsilateral thumb
lpsilateral little finger
mal a m p l i t u d e at intermediate locations 7 a n d 8. The topographic d i s t r i b u t i o n of the m a j o r features at 31 and 56 msec latency is illustrated by ±sopotential m a p s in Fig. 5.
(3) Ipsilateral face interference effect C o n s i s t e n t deflections were also identifiable in the ipsilateral face difference wave form (Figs. 3A a n d 4 a n d T a b l e I), i n d i c a t i n g that the cortical response to m e d i a n nerve s t i m u l a t i o n was significantly altered by c o n c u r r e n t tactile s t i m u l a t i o n of the per±oral area a n d lips ipsilateral to the electrical stimulus. E x a m i n i n g both the group average wave forms of 12 subjects recorded with a n 8c h a n n e l m o n t a g e a n d of 7 subjects recorded with a 16-channel montage, the first consistent peak was a d o w n w a r d deflection (D27) m a x i m a l between C3 a n d P3 (location 8) b u t spreading to all sites over
the left hemisphere and Cz. There was no evidence of a n y inversion of polarity in frontal areas, in contrast to the c o m p o n e n t s of slightly longer latency seen in the t h u m b a n d little finger difference wave forms. A second d o w n w a r d deflection (D52) had a fairly similar distribution, although with a slightly more posterior emphasis a n d less spread towards the m i d l i n e of the scalp. This was very similar to the d i s t r i b u t i o n of D54 in the little finger difference wave form. U p w a r d deflections between D27 a n d D52 (U41) a n d following D52 (U65) were m a x i m a l at C3 in the group average data e m p l o y i n g the 8-channel m o n t a g e (Fig. 3A), b u t in the 16-channel data (Fig. 4) these may simply have reflected a return towards the baseline. I n 2 subjects out of 7, however, U41 a n d U65 were clearly present, with similar d i s t r i b u t i o n s centered on F3 and inter-
A D J A C E N T A N D R E M O T E I N T E R F E R E N C E EFFECTS ON SEPs
(A)
Difference Ipsilateral
little
Waveform
finger
'"-T-"-T'-T"'-I-'-T"-T'-T-'-T"
257
(average
Ipsilateral
12 subjects)
of
palm ' I '1 '"T"
Contralateral
face
"T"-T-'-T'-T'-I-"-T'-T"I
"
'"T"T-"T"-TTT
U~2 D~7
Fpz F3 D59 U68
C3
U45
D69
U65
o4,
C4
I114V
01 02
, ..,....L.,..J.,,,....I ......... I......... I......... 1......... I....L.L_,...
10
(B)
30
50
70 ms
,,.J.,
I .... L,
10
30
I , I ......I....... I......... I......
50
70 ms
, I ,I 10
,I,1,1,1~1 30 50
, I, 70 ms
Ipsilateral little finger i n t e r f e r e n c e e f f e c t ( a v e r a g e of 12 s u b j e c t s )
C3
F3
P3
""T-"T"-T-'I"T"T"
'"T"T"'"'T"'-T"-T'-T'-T-"T-"
I ' 'I "
'I-I"--I-"I-"I"-I"T"T-"-r
--T
I
1 I~V
Difference
....... I......... I......... I......... I......... I......... I......... I......... l........
10
30
50
70 ms
.j,.J.........I.........I.........1.........I.........L.,_J.........I........ 10
30
50
70 ms
......I.........I.........L..,...L_,_..I......I..... L_.,_.I........ 10
30
50
70 ms
Fig. 3. A: group average (12 subjects) of the ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms, 8-channel montage. B: group average (12 subjects) of the ipsilateral little finger 'control,' 'interference' and 'difference' wave forms at F3, C3 and P3.
mediate location 4 (Fig. 6). Topographic maps are illustrated for the 16-channel group average data at 27 and 51 msec (Fig. 5), and subject R.K. at 28, 38, 53 and 68 msec (Fig. 6).
(4) Contralateral palm interference effect A fairly consistent 'difference' wave form was also produced by stimulation of the palm contralateral to the electrically stimulated median nerve. In the study of 12 subjects using the 8-chan-
nel m o n t a g e (Fig. 3A and Table I) at least 2 d o w n w a r d and 1 upward deflections (D27, U45 and D69) were recognized at the F3 electrode, spreading to Fpz. These were clearly reproduced with the 16-channel montage, spreading to location 4 between F3 and C3, and C1 (Fig. 4). D27 differed from the c o m p o n e n t of similar latency in the face difference wave form, having a distribution more confined to frontal and central regions (Fig. 4). The U45 potential was fairly well defined
Difference waveform (average of 7 subjects) Ipsileteral little finger "1'
I'
I'
I'
I
I ' I'1
Ipsileteral '
Contralateral
face
palm
I
F3 . . , ~
c~
~-~ ~
c,
8
II~V
.......I.........I............... I.........I..... I......... ]......... L.,,,, 10 30 50 70 ms
10
30
50
70
ms
10
30
50
70
ms
Fig. 4. G r o u p average (7 subjects) of the ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms, 16-channel montage. Vertical lines are drawn at the latencies of the isopotential m a p s shown in Fig. 5.
Isopotential maps of Difference waveform Ipsilateral little finger
Ipsilateral
face
Contralateral
palm
Fig. 5. Isopotential m a p s of the group average ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms based on the 16-channel data of 7 subjects shown in Fig. 4. D o w n w a r d potentials are denoted by + + + contours (80, 60, 40 and 20% of maximal amplitude), upward potentials by ---, and the zero potential contour by ,,4~1.
ADJACENT AND REMOTE INTERFERENCE EFFECTS ON SEPs in the group average wave form using the 16-channel montage and was remarkably prominent in 2 out of 7 subjects. In these the amplitude of U45 was maximal at C1, spreading to C3, F3 and intermediate locations 4 and 8 (Fig. 7). A single long-duration downward potential (D56) was identifiable at the C3 electrode, merging with D69 at more anterior sites (for example location 4) D56 was also clearly recognized in the 16-channel montage, being maximal at location 8 and spreading to C3 and all sites over the left hemisphere, becoming D69 frontally. D56, therefore, had a similar distribution to components of approximately the same latency (D54 and D52) present in the little finger and face difference wave forms (Fig. 4). As with facial interference, no phase reversal phenomena were apparent when the interfering stimulus was applied to the contralateral palm As indicated above, a comparison of isopoten-
Ipsilateral
face
difference
259
tial maps drawn for difference potentials peaking between 27 and 31 msec after the median nerve stimulus ( F i g 5) revealed marked differences between little finger, face and contralateral palm interference effects. For the little finger there was a clear inversion of polarity between frontal and parietal locations (as was also found with tactile stimulation of the ipsilateral thumb), and the zero potential contour approximately followed the line of the central sulcus at latencies of 23-40 m s e c For the ipsilateral face condition there was no apparent phase reversal, and the downward deflection centred on location 8 spread to all sites except the mastoid process For the contralateral palm condition the downward deflection was located more anteriorly at frontal and central sites: although there was some spread to parietal electrodes, there was no significant downgoing activity below a line approximately overlying the sylvian fissure A much greater degree of similarity existed
waveform
(subject
R.K.)
""T""'T"'"" I"'''r'' T'"'"'T' ""T'"'" T'""'T""" i
F 3 ~,~.//~" 1 ,/~-,-~.,~ ,.,,~
.,, i~/,.r T3
C 5 ~ . :
-J
J
]
11JV
_~..J.........I...... I........J......... I....... l ....... I......... I........ lO 30 50 7 0 ms
Fig 6 Ipsilateral face difference wave form (16-channel montage) and 4 isopotential maps in one subject ( R K )
260
R. KAKIG1, S.J. JONES
Contralateral ''T'T"
difference waveform
palm
(subject K.C.)
.......' " T • ' I T ' I F ' ........' T '
F 7 ~,,_.,...-..n4
Fa
J f C3
jr\
,,-.,~.,_
f
\ J/
J J
/
T 5 ~ . ~ , , _ . . , ~
/ .......I.........I........ I.........L.,LI ....... 10 30 50
k
I.........I....,... 11 p 70
/
ms
Fig. 7, Contralateral palm difference wave form (16-channel montage) and 4 isopotential maps in one subject (K.C.).
Difference waveform Face T-'T'
"T'T'T'
(average of 12 or 8 subjects) Foot
Forearm
T'
T'-T
'
""r
' T ' T - ' - T " T ' " T' ' T '
T '
",r'
I 'T'T'T'T'-T'T'
U41
D22 U36
', ;
U41
U65 032
D 7
?
? lpV
....... I......... I......... I......... I........ I......... I......... I......... I........
10
30 50 I: I p s i l a t e r a l
....... I ......... 1......... I ......... I ......... I ......... I ......... 1......... I ........
10 7 0 ms C : Contralateral
30
50
70
ms
~....I ......... I......... I......... I......... I......... I......... I......... 1........
10
30
50
70
ms
Fig. 8. Group average difference wave forms at F3, C3 and P3 with tactile stimulation of the face, forearm and foot ipsilateral and contralateral to the stimulated median nerve (12 subjects for ipsilateral and 8 subjects for contralateral).
A D J A C E N T A N D REMOTE I N T E R F E R E N C E EFFECTS ON SEPs
between isopotential maps drawn at latencies of 51-59 msec, corresponding with the second downgoing peak. For all 3 interference conditions the peak was maximal over the parietal cortex, spreading to central and temporal regions. For the contralateral palm condition there appeared to be rather more spread to central and frontal electrodes, but this may have been due to confusion between distinct parietal D56 and frontal D69 components.
(5) Interferencefrom other regions of the body surface The tactile interfering stimulus was applied to the forearm and the foot ipsilateral to the stimulated median nerve in 12 subjects, and to the contralateral forearm, face and foot in 8. The difference wave forms derived at F3, P3 and C3 with ipsilateral and contralateral interfering stimulation are shown in Fig. 8. In comparison with the ipsilateral face effect (already described), tactile stimulation of the contralateral perioral area and lips resulted in similar D27 and D52 components in the difference wave form, although both were less well defined. The intervening and following upgoing deflections were much less apparent with the contralateral interfering stimulus. Stimulation of the ipsilateral forearm resulted in a difference wave form in which frontal U41 and centro-parietal D32 components existed concurrently for much of their duration, the former being followed by a D61 and the latter by a D57 peak. With interference from the contralateral forearm the central and parietal difference wave forms were similar to corresponding ipsilateral difference wave forms, although of smaller amplitude. The upward peak at F3, however, was increased in latency by approximately 10 msec, such that there was less suggestion of a polarity inversion relative to C3 and P3. The ipsilateral foot difference wave form consisted of a triphasic pattern at F3 (D22, U36 and D61) and a W-shape at C3 and P3 (D34 and D58). The pattern was very similar when the interfering stimulus was applied to the contralateral foot. In general there was less disparity between difference wave forms obtained with interfering stimulation of the 3 contralateral regions, than between corresponding ipsilateral interference effects.
261
Discussion In a previous study (Jones and Power 1984) the effect of continuous tactile stimulation of the ipsilateral palm on the median nerve SEP was investigated. By subtraction of the 'interference' wave form from the 'control' SEP, a 'difference' wave form was obtained which was highly consistent between individuals. Following parietal 'P'14 and ' N ' 1 9 and frontal 'P'21 potentials, the 2 major components - - 'P'32 and ' N ' 3 6 - - were distributed over the parietal (contralateral) and frontal cortex respectively. Since there was a great deal of temporal overlap between these components, and the zero potential contour closely followed the line of the central sulcus at latencies from 30 to 40 msec, they were considered to be consistent with the field of a dipolar generator oriented in an antero-posterior direction and situated in the region of the central sulcus. The most likely location was thought to be area 3b, which lies in the posterior wall of the central sulcus and is highly responsive to cutaneous stimuli (Powell and Mountcastle 1959). The probable mechanism was considered to be partial 'saturation' of a cortical area concerned with the processing of input from cutaneous mechanoreceptors, such that it was unable to respond fully to the coherent volley evoked by the median nerve impulse. For that reason the difference (control-interference) components were labeled ' P ' and ' N ' according to the usual convention. In the present study, however, it was felt that the assumption that all components were attenuated under all conditions of the interfering stimulus could not be justified, and so the difference potentials were labelled ' U ' and ' D ' without prejudging their true polarity. In the ipsilateral thumb difference wave form, the apparent phase reversals exhibited between D21 and U21, and U34 and D31, were each consistent with the field of a dipolar generator, oriented in an antero-posterior direction and located in the vicinity of the central sulcus. From the nature of the interfering stimulus it can be assumed that this generator was concerned with the processing of input from cutaneous mechanoreceptors in the thumb. The phase reversals seen
262
in the present study, particularly that between D21 and U21, were more nearly complete than those illustrated in the previous paper (Jones and Power 1984), perhaps because a smaller area of cortex was activated. The morphology of the primary cortical evoked response is positive-negative diphasic at the surface and negative-positive at depth (Bartley and Bishop 1933; Li et al. 1956; Mountcastle et al. 1957), so the distribution and polarity of the early components in the thumb difference wave form are consistent with the primary response of a cortical generator situated in the posterior bank of the central sulcus and partially 'saturated' by continuous tactile input. A model based on dipolar cortical generators was proposed by Broughton (dissertation 1967) and elaborated by Allison et al. (1980) to account for the N 2 0 / P 2 0 and P 3 0 / N 3 0 components of the conventional human SEP, although the phase reversals are not clearly seen in the majority of subjects. In primates the primary sensory cortex (SI) can now be subdivided into 4 regions, corresponding to cortical areas 1, 2, 3a and b (see Kaas et al. 1981). Area 3a has been shown to be a receiving area for muscle spindle afferents (Phillips et al. 1971) and is therefore assumed to be concerned with the processing of proprioceptive information. Area 2 was found to be responsive to stimulation of 'deep' (non-cutaneous) bodily tissues (Powell and Mountcastle 1959; Paul et al. 1972), and therefore is also likely to be mainly concerned with proprioception. Units in areas 1 and 3b, however, respond mainly to cutaneous stimuli (Powell and Mountcastle 1959; Paul et al. 1972; Werner and Whitsel 1973; Kaas et al. 1981). In higher primates area 3b is situated on the posterior bank of the central sulcus, whereas area 1 is largely on the crown of the postcentral gyrus (Fig. 9). The most likely generator of the D 2 1 / U 3 4 and U 2 1 / D 3 1 components of the thumb difference wave form, therefore, was considered to be area 3b. In the little finger difference wave form, U32 at the F3 electrode and D31 at P3 were similar to potentials present in the thumb difference wave form (Figs. 2 and 3) and the zero potential contour at this latency approximately followed the line of the central sulcus (Fig. 5). It seems reasonable to propose, therefore, that the early components of
R, KAKIGI, S.J. JONES
the little finger difference wave form might reflect an attenuation of potentials generated in area 3b, as for corresponding peaks in the thumb difference wave form. This may be analogous to the phenomenon of 'surround inhibition' described by Mountcastle and Powell (1959) with regard to single unit responses in the sensory cortex of the monkey. In the present study, however, it was observed that the SEP might be modified by continuous tactile stimulation of the ipsilateral face and foot and regions of the contralateral body surface also, suggesting that there may be an influence from all areas of the skin on cortical elements responding to median nerve input. The distribution of early components in the difference wave form was considerably different for the face and the contralateral palm as compared with the ipsilateral thumb and little finger, suggesting that the interaction may take place in different areas of cortex. in the ipsilateral face difference wave form the D27 potential was widely distributed over frontal, parietal and central regions, being maximal just anterior to the P3 electrode with no evidence of phase reversal. In the contralateral palm d~fference wave form there was also no evidence of phase reversal, but the D27 potential had a more frontal distribution and was not recorded over the temporal cortex below a line approximately overlying the sylvian fissure. The facial region of area 3b is situated on the posterior bank of the inferior part of the central sulcus and is adjacent to the second sensory area, SII. In primates the facial region of the latter is located on the crown of the superior bank of the sylvian fissure (Whitsel et al. 1969; see Fig. 9). Therefore, the distribution of D27 in the face difference wave form was more consistent with a generator in the facial region of SI or SI1 than with the hand region of area 3b. In the contralateral palm difference wave form, the distribution of D27 was perhaps most consistent with a generator in the hand area of SII, which in primates is situated in the superior bank of the sylvian fissure (Whitsel et al. 1969; Fig. 9). The dipolar elements of such a generator would be oriented towards the frontal cortex (where D27 was maximal) and the inferior temporal lobe. Since no phase reversal phenomena were apparent be-
A D J A C E N T A N D R E M O T E I N T E R F E R E N C E EFFECTS ON SEPs
sulcus~..___
Central
~!~n
..
...... ~g
~ *
'.. S1(3,2,1)."Syl vian~,K'~]rA_r~:| ~'~I fissure~~ .............~Tempor lobe
Fig. 9. Schematic representat=on of sensory cortical areas in m a n (after Foerster 1936), showing probable location of SI (arranged from Kaas et al. 1981), SII (arranged from Whitsel et al. 1969) and parietal association areas.
tween precentral and infero-temporal electrodes, however, a generator in precentral cortex adjacent to the site at which D27 was of maximal amplitude is another possibility which cannot be excluded. Neurons in SII differ from those in SI in that their receptive fields are larger, encompassing ipsilateral as well as contralateral areas of the body surface for 63% of units studied in unanesthetized cats (Robinson 1973) and 90% of units in unanesthetized monkeys (Whitsel et al. 1969). Neurons in SII are also particularly responsive to light touch stimulation: Whitsel et al. (1969) reported that 87% of neurons in the SII area of unanesthetized monkeys were activated by cutaneous light touch stimulation. Jones and Powell (1969, 1970), reviewing previous papers, suggested that SII might be an area for interhemispheric convergence of sensory input of all somatic modalities at a relatively low level of cortical function. Although previous reports contain no description of units with receptive fields encompassing such widely separated regions as the hand and the face, their conclusions are broadly compatible with the findings of the present study. The potentials of latency longer than 50 msec were similar for each difference wave form (principally the little finger, face and contralateral palm) except the ipsilateral thumb. The isopotential maps
263
of the second downward potential, D54 for the little finger, D52 for the face and D55 for the contralateral palm, showed very similar distributions, with maxima in the parietal region just anterior to P3 and spreading to all sites in the 16-channel montage but with smaller amplitude in frontal and temporal regions (Figs. 4 and 5). A likely generator for these potentials would be the parietal 'association' cortex, areas 5 a n d / o r 7 (nomenclature of Vogt and Vogt, see Foerster 1936). Although the detailed (16-channel) topographic study was not performed for the thumb, U65 in the difference wave form appeared to be of similar distribution to D54, D52 and D55 in the ipsilateral little finger, face and contralateral pahn difference wave forms, respectively. U65 also, therefore, might be generated in areas 5 a n d / o r 7. Examination and comparison of 'control' and 'interference' wave forms suggests that, whereas U65 may reflect a negative-going component which is attenuated in the thumb interference wave form (see Fig. 2), D54, D52 and D56 may conversely be due to enhancement of a slightly earlier negativity when the interfering stimulus is applied to regions of the body surface outside the sensory distribution of the median nerve (see Fig. 3B). In conclusion, the interference technique has been used to demonstrate interaction between sensory inputs from various parts of the body, manifested in the responses of 'primary' (SI and SII) and 'association' cortical areas. Whereas animal work has done much to elucidate the analytical processes involved with sensation, the SEP technique may prove a more appropriate tool for studying integrative mechanisms which are of equal importance in the context of relating various parts of the body to one another
Resume
Effets sur les P E S du nerf mbdian de stimulations tactiles appliqukes gt des aires adjacentes ou bloignkes de la surface du corps
L'6tude de l'influence de stimulations tactiles continues sur les potentiels 6voqu6s somatosensoriels (PES) produits par la stimulation 61ectrique
264
du nerf m6dian r6v61e un effet dfa h des interf6rences en provenance de r6gions adjacentes et 61oign6es de la surface du corps. La distribution de cet effect a 6t6 6valu6 en soustrayant la r6ponse avec 'interf6rence' de la r6ponse 't6moin' pour obtenir une forme d'onde de 'diff6rence'. La stimulation tactile du pouce ipsilat6ral h la stimulation du nerf m6dian produisait une onde de diff6rence dans laquelle un net renversement de phase 6tait apparent entre les aires pr6- et postcentrale pour 2 complexes, aux latences approximatives de 20 et 30 msec. Peut Etre 6tait-ce dfa /~ une saturation partielle d'un g6n6rateur dans la r6gion de la main de l'aire 3b du cortex somatosensoriel (SI), lequel 6tait alors incapable de r6pondre enti6rement aux influx du nerf m6dian. Un effect similaire a 6t6 observ6 lorsque le stimulus interf6rant 6tait appliqu6 h l'auriculaire ipsilat6ral, refl6tant probablement un processus d'inhibition lat6rale. La stimulation tactile de r6gions plus 61oign6es (principalement de la figure et de la main contralat6rale) fournit des coubes de diff6rence nettes dans lesquelles des composantes pr6coces (latence inf6rieure a 30 msec) ont des distributions de scalp diff6rentes les unes des autres mais en accord avec une influence sur des g6n6rateurs dans la r6gion de la face ou de la main du cortex somatosensoriel secondaire (SII). Des potentiels tardifs bien identifiables dans les courbes de diff6rence 6taient similaires quelle que soit la localisation du stimulus interf6rent sauf le pouce ipsilat6ral et 6talent distribu6s en conformit6 avec l'hypoth6se d'un g6n6rateur dans le cortex associatif pari6tal. We are grateful to Dr. A.M. Halliday for his advice and criticism of the manuscript.
References Allison, T., Golf, W.R., Williamson, P.D. and Van Gilder, J.C. On the neural origin of early components of the h u m a n somatosensory evoked potential. In: J.E. Desmedt (Ed.), Clinical Uses of Cerebral, Brainstem and Spinal Somatosensory Evoked Potentials. Prog. clin. Neurophysiol., Vol. 7. Karger, Basel, 1980: 51-68. Bartley, S.H. and Bishop, G.H. The cortical response to stimulation of the optic nerve in the rabbit. Amer. J. Physiol., 1933, 133: 159-172.
R. K A K I G I , S.J. JONES Carreras, M. and Andersson, S.A. Functional properties of neurons of the anterior ectosylvian gyrus of the cat. J. Neurophysiol., 1963, 26: 100-126. Foerster, O. Symptomatologie der Erkrankungen des Grosshirns. In: O. Bumke und O. Foerster (Eds.), Handbuch der Neurologie, Vol. 6, Springer, Berlin, 1936: 1-448. Giblin, D.R. Somatosensory evoked potentials in healthy subjects and in patients with lesions of the nervous system. Ann. N.Y. Acad. Sci., 1964, 112: 93-142. Jones, E.G. and Powell, T.P.S. Connections of the somatic sensory cortex of the rhesus monkey. I. lpsilateral cortical connections. Brain, 1969, 92:477 502. Jones, E.G. and Powell, T.P. An anatomical study of converging sensory pathways within the cerebral cortex of the monkey. Brain, 1970, 93:793 820. Jones, S.J. An 'interference' approach to the study of somatosensory evoked potentials in man. Electroenceph. clin. Neurophysiol., 1981, 52: 517-530. Jones, S.J. and Power, C. Scalp topography of h u m a n somatosensory evoked potentials: the effect of interfering tactile stimulation applied to the hand. Electroenceph. clin. Neurophysiol., 1984, 58:25 36. Kaas, J.H., Nelson, R.J., Sur, M. and Merzenich, M.M. Organization of somatosensory cortex in primates. In: F.O. Schmin, F.G. Worden, G, Adelman and S.G. Dennis (Eds.), The Organization of the Cerebral Cortex. MIT Press, Cambridge, MA, 1981: 237-261. Kakigi, R. and Shibasaki, H. Scalp topography of mechanically and electrically evoked somatosensory potentials in man. Electroenceph. clin. Neurophysiol., 1984, 59: 44-56. Li, C.-L., Cullen, C. and Jasper, H.H. Laminar microelectrode studies of specific somatosensory cortical potentials. J. Neurophysiol., 1956, 19: 111-130. Mark, R.F. and Steiner, J. Cortical projection of impulses in myelinated cutaneous afferent nerve fibres of the cat. J. Physiol. (Lond.), 1958, 142:544 562. Mountcastle, V.B. and Powell, T.P.S. Neural mechanisms subserving cutaneous sensibility: with special reference to the role of afferent inhibition in sensory perception and discrimination. Bull. Johns Hopk. Hosp., 1959, 105: 201-232. Mountcastle, V.B., Davies, P.W. and Berman, A.L. Response properties of neurons of cat's somatic sensory cortex to peripheral stimuli. J. Neurophysiol., 1957, 20: 374-407. Paul, R.L., Merzenich, M. and Goodman, H. Representation of slowly and rapidly adapting cutaneous mechanoreceptors of the hand in Brodmann's area 3 and 1 of Macaca mulatta. Brain Res., 1972, 36: 229-249. Phillips, C.G., Powell, T.P.S. and Wiesendanger. M. Projection from low threshold muscle afferents of hand and forearm to area 3a of baboon's cortex. J. Physiol. (Lond.), 1971, 217: 419-446. Powell, T.P.S. and Mountcastle, V.B. Some aspects of the functional organization of the cortex of the postcentral gyrus of the monkey: a correlation of findings obtained in a single unit analysis with cytoarchitecture. Bull. Johns Hopk. Hosp., 1959, 105: 133-162. Robinson, D.L. Electrophysiological analysis of interhemi-
ADJACENT A N D REMOTE INTERFERENCE EFFECTS ON SEPs spheric relations on the second somatosensory cortex of the cat. Exp. Brain Res.~ 1973~ 18: 131-144. Vallbo, A.B., Hagbarth, K.E., Torebj6rk, H.E. and Wallin, B.G. Somatosensory, proprioceptive and sympathetic activity in human peripheral nerves. Physiol. Rev., 1979, 59: 919-957. Werner, G. and Whitsel, B.L. Functional organization of the
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somatosensory cortex. In: A. Iggo (Ed.), Handbook of Sensory Physiology~ Vol. 2. Springer, Berlin, 1973: 621-700. Whitsel, B.L., Perrucelli, L. and Werner, G. Symmetry and connectivity in the map of the body surface in somatosensory area Ii of primates. J. Neurophysiol., 1969, 32: 170-183.
Electroencephalograph), and clinical Neurophysiologr', 1985, 62:252-265
Elsevier Scientific Publishers Ireland, Ltd.
EFFECTS ON MEDIAN NERVE SEPs OF TACTILE AND REMOTE AREAS OF THE BODY SURFACE
STIMULATION
APPLIED
TO
ADJACENT
RYUSUKE KAK1GI 1 and S.J. JONES Medical Research Council, National Hospital for Nervous Diseases, Queen Square, London W C I N 3BG ( U.K.)
(Accepted for publication: January 26, 1985)
Summary Study of the influence of continuous tactile stimulation on somatosensory evoked potentials (SEPs) following electrical stimulation of the median nerve revealed an effect due to interfering input from both adjacent and remote regions of the body surface. The distribution of the effect was demonstrated by subtracting the 'interference' from the 'control' response to derive a 'difference' wave form. Tactile stimulation of the thumb ipsilateral to the stimulated median nerve produced a difference wave form in which a marked phase reversal was apparent between pre- and post-central areas for 2 complexes, at latencies of approximately 20 and 30 msec. It is proposed that this may have been due to partial 'saturation' of a generator in the hand region of area 3b in the primary somatosensory cortex (SI), which was then unable to respond fully to the median nerve impulse. A similar effect was observed when the interfering stimulus was applied to the ipsilateral little finger, possibly reflecting a process of 'surround inhibition.' Tactile stimulation of more remote regions (principally the face and contralateral hand) resulted in consistent difference wave forms in which the early components (less than 30 msec latency) had scalp distributions differing from one another but consistent with influence on generators in the face or hand region of the second somatosensory cortex (SII). Later potentials consistently identifiable in the difference wave forms were similar for all locations of the interfering stimulus apart from the ipsilateral thumb and were distributed in accordance with a proposed generator in the parietal 'association' cortex. Keywords: somatosenso O' evoked potentials ( S E P s ) - - electrical and mechanical stimulation
tactile interference - -
mechanorecep-
tors - - S I and S I I cortical areas - - parietal association cortex
O n e of the m a j o r p r o b l e m s in the i n t e r p r e t a t i o n of conventional somatosensory evoked potentials ( S E P s ) f o l l o w i n g electrical s t i m u l a t i o n of the m e d i a n n e r v e at t h e wrist is t h a t fibers s e r v i n g m o r e t h a n o n e s e n s o r y m o d a l i t y a n d p r o j e c t i n g to d i f f e r e n t a r e a s o f c o r t e x are s t i m u l a t e d s i m u l t a n e o u s l y . R e c e n t a d v a n c e s in m i c r o n e u r o g r a p h y h a v e d e m o n s t r a t e d that the h u m a n m e d i a n n e r v e c o n t a i n s large d i a m e t e r a f f e r e n t fibers of m a n y types, r e s p o n d i n g to s t i m u l i such as d e f o r m a t i o n o f the skin, p a s s i v e m u s c l e stretch, v o l u n t a r y c o n t r a c t i o n , d e e p p r e s s u r e o r v i b r a t i o n (see V a l l b o et al. 1979). T h e p r i m a r y s o m a t o s e n s o r y c o r t e x (SI) is n o w k n o w n to c o n t a i n at least 4 r e p r e s e n t a t i o n s o f the b o d y , c o r r e s p o n d i n g to areas 1, 2, 3a a n d 3b, e a c h o f w h i c h a p p e a r s to b e a s s o c i a t e d w i t h s e n s o r y i n p u t of a p a r t i c u l a r m o d a l i t y o r c o m b i n a Ryusuke Kakigi was supported by a Research Fellowship from the Wellcome Trust in the United Kingdom.
t i o n o f m o d a l i t i e s (see K a a s et al. 1981). In a d d i t i o n , the s e c o n d a r y s o m a t o s e n s o r y c o r t e x (SIt), w h i c h in m o n k e y s is s i t u a t e d o n the s u p e r i o r b a n k o f the sylvian fissure, is k n o w n to c o n t a i n units w h i c h are a c t i v a t e d by light t o u c h a p p l i e d to the skin o f the ipsilateral, as well as the c o n t r a l a t e r a l b o d y s u r f a c e ( M a r k a n d S t e i n e r 1958; C a r r e r a s a n d A n d e r s s o n 1963; W h i t s e l et al. 1969; R o b i n son 1973). T w o d i f f e r e n t m e t h o d s h a v e b e e n a d o p t e d in o r d e r to try to i d e n t i f y S E P c o m p o n e n t s specifically a s s o c i a t e d w i t h the p r o c e s s i n g o f i n p u t f r o m c u t a n e o u s m e c h a n o r e c e p t o r s . O n e is to s t u d y p o t e n t i a l s e v o k e d b y m e c h a n i c a l s t i m u l a t i o n of the b o d y s u r f a c e (see K a k i g i a n d S h i b a s a k i 1984). A n a l t e r n a t i v e a p p r o a c h is to see h o w e l e c t r i c a l l y e v o k e d S E P s are a f f e c t e d by c o n t i n u o u s ' i n t e r f e r i n g ' tactile stimuli a p p l i e d to the skin ( G i b l i n 1964; J o n e s 1981; J o n e s a n d P o w e r 1984). In a p r e v i o u s s t u d y ( J o n e s a n d P o w e r 1984) the
0168-5597/85/$03.30 © 1985 Elsevier Scientific Publishers Ireland, Ltd.
A D J A C E N T A N D R E M O T E I N T E R F E R E N C E EFFECTS ON SEPs
253
electrical stimulus was delivered to the median nerve and the interfering stimulus to the ipsilateral palm. By subtracting the 'interference' wave form so obtained from a 'control' wave form, a 'difference' wave form was derived in which the 2 major components were a positivity, maximal over the contralateral parietal cortex, and a negativity of similar latency and duration with a fairly symmetrical distribution in frontal regions. It was proposed that these might be attributable to a single generator situated in the posterior bank of the central sulcus, corresponding to area 3b. In an earlier study (Jones 1981) there was a suggestion that SEPs might also be influenced by light touch stimulation of other parts of the body. The object of the present investigation, therefore, was to examine changes in the wave form of conventional electrically evoked SEPs, produced by continuous tactile stimulation of various parts of the body such as the face, hand, forearm and foot ipsilateral and contralateral to the stimulated median nerve.
Material and Methods Fourteen normal volunteers, 10 men and 4 women, were studied. Their ages ranged from 19 to 35 years with a mean age of 31. Their height ranged from 152 to 184 cm (mean 168). Recordings were performed in a quiet room. The subject was sealed comfortably in a reclining arm-chair and was encouraged to relax. No medication was given and the subject was kept awake. The electrical stimulus was a constant voltage square-wave impulse delivered to the right median nerve at the wrist. The stimulus duration was 0.2 msec, the intensity sufficient to produce a definite twitch of the thumb and the frequency 5/sec. In the initial study of 12 subjects, 8 recording electrodes were attached to the scalp at locations Fpz, F3, C3, Cz, C4, P3, O1 and 0 2 of the 10-20 system. A separate and more detailed topographical study was made in 7 subjects with 16 electrodes located over the scalp contralateral to the stimulus, at F7, F3, T3, C5, C3, C1, T5, P3 and additional locations 1-8 as shown in Fig. 1. Location 1 was just anterior to the tragus and
Fig. 1. Electrode placements used for the 8- and 16-channel montages. Location 1 was ~ust anterior to the tragus, location 5 on the mastoid process and the reference on the right earlobe (A2).
location 5 at the mastoid process. All sites were referred to A2 (right earlobe). The high-frequency response of the amplifier was less than 3 dB down at 5 kHz and the time constant was 1 sec. The average of 1000 responses was computed, on 8 or 16 channels simultaneously, using a digital averager with an epoch of 85 msec starting 3 msec after the stimulus and a sampling interval of 0.33 msec. Continuous light tactile stimulation was delivered by the experimenter concurrently with the median nerve stimulus, using a soft wad of tissue paper or a manually rotated cylinder (diameter 4 cm) covered in wool carpeting. Tissue paper was used to stimulate the pad of the thumb and little finger, the forearm, face (perioral areas and lips)
254
R. KAKIGI, S.J. JONES
and the sole of the foot ipsilateral to the stimulated median nerve, and the face, forearm and foot on the contralateral side. The contralateral palm was stimulated by means of the cylinder, loosely resting in contact with the thumb and the 2nd and 3rd digits and rotated at 1 - 2 rev/sec. In the initial series of 12 subjects, using the 8-channel montage, 2 or 3 average responses were recorded of the 'control' SEP (without tactile interference) and of 'interference' SEPs with continuous tactile stimulation of each skin area ipsilateral to the median nerve stimulus, and the contralateral palm. The remaining contralateral regions were stimulated ill 8 subjects. In the second series of 7 subjects, for whom the 16-channel montage was employed, 4 average responses were recorded of the 'control' SEP and of 'interference' SEPs with continuous tactile stimulation of the ipsilateral little finger, the ipsilateral face and the contralateral palm. The order of the 'control' and 'interference' conditions was alternated to control for long-term trends throughout the recording session. Grand average wave forms were computed for each stimulus condition in each subject and then combined in group average wave forms. Isopotential maps were plotted from the 16channel group average difference wave forms, at intervals of 1 msec between 14 and 78 msec following the stimulus. Peak latencies and peak-to-peak amplitudes were measured for consistently identifiable components.
attenuated or enhanced under the interference condition. The overall trend was best demonstrated by subtracting the 'interference' from the 'control' wave form, but the peaks seen in the 'difference' wave form did not correspond precisely in latency with potentials identified in the directly obtained wave forms. Consequently it was not possible to explain the difference peaks simply in terms of attenuation or enhancement of potentials in the conventional median nerve response. In the difference wave form the following components were identifiable ( ' U ' signifying an upward deflection and ' D ' downward, see Table l): U21 and D31 potentials at the P3 electrode spreading to O1, 0 2 and (D31 only) C3; U65 and D85 at C3 spreading to P3 and O1; D21, U34, D57 and U78 at F3, the last 3 spreading to Fpz. A small downward potential, DI4, was recognized at the Ol and 0 2 locations but was absent at more frontal electrodes. The U21 and D31 components recorded at P3 demonstrated an apparent phase reversal with D21 and U34 respectively at F3, although U34 was of slightly longer duration and peak latency than D31. U65 recorded at C3 and P3 overlapped in duration with D57 recorded at F3, the peak latencies differing by 8-10 msec. No significant difference potentials were present at Cz or C4 except for some spread of U34 at Cz. These effects were very similar to those produced by stimulating the whole of the palm (Jones and Power 1984), and so were not studied further using the 16-channel montage.
Results
(2) Ipsilateral little finger interference effect
(1) lpsilateral thumb interference effect The most consistent and reproducible interference effect amongst all conditions of the present study was obtained with tactile stimulation of the thumb ipsilateral to the electrically stimulated median nerve. Fig. 2 shows the group average 'control,' 'interference' and 'difference' wave forms obtained with the 8-channel montage from 12 subjects. Although clear differences can be seen between the control and interference conditions, apparently reflecting attenuation of some components and enhancement of others, it could not be stated categorically that the wave form was either
With continuous tactile stimulation of the little finger ipsilateral to the electrically stimulated median nerve, consistent differences were also present between the 'control' and 'interference' wave forms. As for the thumb interference effect, however, these appeared to consist of attenuation of some components and enhancement of others, and the overall effect was more clearly revealed in the 'difference' wave form (Fig. 3A and Table I). At F3 an ill-defined downward potential peaking at 23 msec was followed by consistent U32 and D59 components, similar to components present in the ipsilateral thumb difference wave form. At the P3 electrode an ill-defined upward deflection
ADJACENT AND REMOTE INTERFERENCE EFFECTS ON SEPs Ipsilateral
thumb
interference
Control .....
'"T"-T'T"-T'-T'T"'"T'"'""r'
255
effect
(average
Interference 'T""'T'T"'"'T'"'""r'"'""r'"'"'T'"""T
.....
TM
of
12
subjects)
Difference '""I'"""T'"'"'T'"'"'T'"'"'T'"""T'"'"'T'"'"'T'"'"' U34
Fpz F3
D21
D57
U65 C3
Cz C4
I IJ.V P3 01 02
......I.........I.........I.........I.........I.........I.........I.........I............... I.........I.........I.........I.........I.........I.........I.........I........ 10
30
50
70
ms
10
30
50
70
ms
.......I.........I.........I......... I.........I.........I......... I.........I........ 10 30 50 7 0 ms
Fig. 2. Group average wave forms (12 subjects) of the 'control' (without interference), 'interference" (with continuous tactile stimulation applied to the right thumb) and 'difference' (derived by subtraction of the 'interference' from the "control' wave form) SEPs, 8-channel montage. Stimulation of the fight median nerve at the wrist with the right earlobe (A2) as reference and negativity at grid 1 upward in this and all following figures. p e a k i n g at a p p r o x i m a t e l y 20 msec was followed by a consistent D31 s p r e a d i n g to O1 a n d 0 2 , a n d similar to D31 in the t h u m b difference wave form. D31 at P3, therefore, d e m o n s t r a t e d an a p p a r e n t p h a s e reversal with U32 at F3. T h e difference wave form at C3 consisted of a d o w n g o i n g p e a k (D26) which a p p e a r e d to be a c o m p o s i t e of p o t e n tials present at P3 a n d F3. F o l l o w i n g a return t o w a r d s the baseline a second d o w n w a r d p e a k (D54) was m a x i m a l at C3, s p r e a d i n g to P3 a n d O1. N o similar p o t e n t i a l was consistently identifiable in the t h u m b difference wave form. D54 was followed b y an u p w a r d p e a k (U68) with a similar d i s t r i b u t i o n , c o m p a r a b l e with U65 in the t h u m b difference wave form a l t h o u g h of m u c h smaller amplitude. T h e m a i n features of the ipsilateral little finger
difference wave form were c o n f i r m e d in 7 subjects using a m o n t a g e of 16 electrodes over the left hemisphere, referred to the right ear lobe (Fig. 4). A d d i t i o n a l l y , an initial u p w a r d p e a k (U20) and d o w n w a r d p e a k (D22) were m o r e clearly identifiable, the former w i d e s p r e a d over the p o s t e r i o r q u a d r a n t a n d the latter present at C1, C3 and i n t e r m e d i a t e location 4. As in the 8-channel d a t a U32 was m a x i m a l at F3, b u t was also p r e s e n t at a d j a c e n t sites ( i n t e r m e d i a t e location 4 a n d C1). D31 was again m a x i m a l at P3, s p r e a d i n g to all sites in the p o s t e r i o r q u a d r a n t a n d also to C5 a n d T3. A t C3 the early p a r t of the wave form was t r a n s i t i o n a l between that r e c o r d e d a n t e r i o r l y and posteriorly, b u t in this g r o u p of subjects no D26 p o t e n t i a l was a p p a r e n t . D54 was widely distribu t e d at central a n d parietal locations, with maxi-
256
R. KAKIGI, S.J. JONES
TABLE I Peak latency and amplitude of each consistently recognizable component maximally recorded at the F3, C3 and P3 electrodes (8-channel montage) in the ipsilateral thumb, ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms, Electrode site
Potential
Number of subjects
Mean latency _+1 S.D. (msec)
Latency of group averagewave form (msec)
Mean amplitude _+1 S.D. (/*V)
F3
D21 U34 D57 U78
12/12 12/12 12/12 11/12
20.9 ± 1.9 32.8 ± 3.1 55.9 _+7.3 73.9 ± 6.4
21.0 33.6 57.3 78.0
0.5 ± 0.2 1.2 ± 0.3 1.4 _+0.7 1.1 ± 0.6
C3
U65 D85
9/12 7/12
66.2 _+6.0 79.9_+6.3
65.2 85.0
1.8 + 0.8 1.9 ± 0.8
P3
U21 D31
12/12 12/12
21.4 _+2.2 32.4 ± 3.1
20.5 31.1
0.4 ± 0.3 1.4 + 0.7
F3
U32 D59
12/12 12/12
32.5 _+3.1 58.8 _+5.0
31.9 59.1
0.8 + 0,5 1.3 + 0.7
C3
D26 D54 U68
11/12 12/12 12/12
26.1 ± 3.1 52.4_+4.6 68.8 ± 7.6
25.8 53.5 68.2
0.7 ± 0,5 1.2 ± 1,0 1.3 _+1.0
P3
D31
11/12
29.0 ± 3.6
30.8
1.0 ± 0.6
Ipsilateral face
C3
D27 U41 D52 U65
12/12 10/12 11/12 10/12
27.1 _+3.7 40.3 ± 5.1 52.8_+4.4 68.8 ± 6.4
27.0 40.6 51.3 64.4
0.8 ± 0.4 1.2 ± 0.6 1.1 _+0.5 1.2 + 0.9
Contralateral palm
F3
D27 U45 D69
11/12 11/12 11/12
28.2 _+2.9 45.1 ± 6.5 64.9 _+7.4
26.8 44.9 68.5
0.5 ± 0.4 0.8 _+0.4 1.1 ± 0.6
C3
D56
12/12
57.2 ± 7.1
55.7
1.3 ± 0.5
Ipsilateral thumb
lpsilateral little finger
mal a m p l i t u d e at intermediate locations 7 a n d 8. The topographic d i s t r i b u t i o n of the m a j o r features at 31 and 56 msec latency is illustrated by ±sopotential m a p s in Fig. 5.
(3) Ipsilateral face interference effect C o n s i s t e n t deflections were also identifiable in the ipsilateral face difference wave form (Figs. 3A a n d 4 a n d T a b l e I), i n d i c a t i n g that the cortical response to m e d i a n nerve s t i m u l a t i o n was significantly altered by c o n c u r r e n t tactile s t i m u l a t i o n of the per±oral area a n d lips ipsilateral to the electrical stimulus. E x a m i n i n g both the group average wave forms of 12 subjects recorded with a n 8c h a n n e l m o n t a g e a n d of 7 subjects recorded with a 16-channel montage, the first consistent peak was a d o w n w a r d deflection (D27) m a x i m a l between C3 a n d P3 (location 8) b u t spreading to all sites over
the left hemisphere and Cz. There was no evidence of a n y inversion of polarity in frontal areas, in contrast to the c o m p o n e n t s of slightly longer latency seen in the t h u m b a n d little finger difference wave forms. A second d o w n w a r d deflection (D52) had a fairly similar distribution, although with a slightly more posterior emphasis a n d less spread towards the m i d l i n e of the scalp. This was very similar to the d i s t r i b u t i o n of D54 in the little finger difference wave form. U p w a r d deflections between D27 a n d D52 (U41) a n d following D52 (U65) were m a x i m a l at C3 in the group average data e m p l o y i n g the 8-channel m o n t a g e (Fig. 3A), b u t in the 16-channel data (Fig. 4) these may simply have reflected a return towards the baseline. I n 2 subjects out of 7, however, U41 a n d U65 were clearly present, with similar d i s t r i b u t i o n s centered on F3 and inter-
A D J A C E N T A N D R E M O T E I N T E R F E R E N C E EFFECTS ON SEPs
(A)
Difference Ipsilateral
little
Waveform
finger
'"-T-"-T'-T"'-I-'-T"-T'-T-'-T"
257
(average
Ipsilateral
12 subjects)
of
palm ' I '1 '"T"
Contralateral
face
"T"-T-'-T'-T'-I-"-T'-T"I
"
'"T"T-"T"-TTT
U~2 D~7
Fpz F3 D59 U68
C3
U45
D69
U65
o4,
C4
I114V
01 02
, ..,....L.,..J.,,,....I ......... I......... I......... 1......... I....L.L_,...
10
(B)
30
50
70 ms
,,.J.,
I .... L,
10
30
I , I ......I....... I......... I......
50
70 ms
, I ,I 10
,I,1,1,1~1 30 50
, I, 70 ms
Ipsilateral little finger i n t e r f e r e n c e e f f e c t ( a v e r a g e of 12 s u b j e c t s )
C3
F3
P3
""T-"T"-T-'I"T"T"
'"T"T"'"'T"'-T"-T'-T'-T-"T-"
I ' 'I "
'I-I"--I-"I-"I"-I"T"T-"-r
--T
I
1 I~V
Difference
....... I......... I......... I......... I......... I......... I......... I......... l........
10
30
50
70 ms
.j,.J.........I.........I.........1.........I.........L.,_J.........I........ 10
30
50
70 ms
......I.........I.........L..,...L_,_..I......I..... L_.,_.I........ 10
30
50
70 ms
Fig. 3. A: group average (12 subjects) of the ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms, 8-channel montage. B: group average (12 subjects) of the ipsilateral little finger 'control,' 'interference' and 'difference' wave forms at F3, C3 and P3.
mediate location 4 (Fig. 6). Topographic maps are illustrated for the 16-channel group average data at 27 and 51 msec (Fig. 5), and subject R.K. at 28, 38, 53 and 68 msec (Fig. 6).
(4) Contralateral palm interference effect A fairly consistent 'difference' wave form was also produced by stimulation of the palm contralateral to the electrically stimulated median nerve. In the study of 12 subjects using the 8-chan-
nel m o n t a g e (Fig. 3A and Table I) at least 2 d o w n w a r d and 1 upward deflections (D27, U45 and D69) were recognized at the F3 electrode, spreading to Fpz. These were clearly reproduced with the 16-channel montage, spreading to location 4 between F3 and C3, and C1 (Fig. 4). D27 differed from the c o m p o n e n t of similar latency in the face difference wave form, having a distribution more confined to frontal and central regions (Fig. 4). The U45 potential was fairly well defined
Difference waveform (average of 7 subjects) Ipsileteral little finger "1'
I'
I'
I'
I
I ' I'1
Ipsileteral '
Contralateral
face
palm
I
F3 . . , ~
c~
~-~ ~
c,
8
II~V
.......I.........I............... I.........I..... I......... ]......... L.,,,, 10 30 50 70 ms
10
30
50
70
ms
10
30
50
70
ms
Fig. 4. G r o u p average (7 subjects) of the ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms, 16-channel montage. Vertical lines are drawn at the latencies of the isopotential m a p s shown in Fig. 5.
Isopotential maps of Difference waveform Ipsilateral little finger
Ipsilateral
face
Contralateral
palm
Fig. 5. Isopotential m a p s of the group average ipsilateral little finger, ipsilateral face and contralateral palm difference wave forms based on the 16-channel data of 7 subjects shown in Fig. 4. D o w n w a r d potentials are denoted by + + + contours (80, 60, 40 and 20% of maximal amplitude), upward potentials by ---, and the zero potential contour by ,,4~1.
ADJACENT AND REMOTE INTERFERENCE EFFECTS ON SEPs in the group average wave form using the 16-channel montage and was remarkably prominent in 2 out of 7 subjects. In these the amplitude of U45 was maximal at C1, spreading to C3, F3 and intermediate locations 4 and 8 (Fig. 7). A single long-duration downward potential (D56) was identifiable at the C3 electrode, merging with D69 at more anterior sites (for example location 4) D56 was also clearly recognized in the 16-channel montage, being maximal at location 8 and spreading to C3 and all sites over the left hemisphere, becoming D69 frontally. D56, therefore, had a similar distribution to components of approximately the same latency (D54 and D52) present in the little finger and face difference wave forms (Fig. 4). As with facial interference, no phase reversal phenomena were apparent when the interfering stimulus was applied to the contralateral palm As indicated above, a comparison of isopoten-
Ipsilateral
face
difference
259
tial maps drawn for difference potentials peaking between 27 and 31 msec after the median nerve stimulus ( F i g 5) revealed marked differences between little finger, face and contralateral palm interference effects. For the little finger there was a clear inversion of polarity between frontal and parietal locations (as was also found with tactile stimulation of the ipsilateral thumb), and the zero potential contour approximately followed the line of the central sulcus at latencies of 23-40 m s e c For the ipsilateral face condition there was no apparent phase reversal, and the downward deflection centred on location 8 spread to all sites except the mastoid process For the contralateral palm condition the downward deflection was located more anteriorly at frontal and central sites: although there was some spread to parietal electrodes, there was no significant downgoing activity below a line approximately overlying the sylvian fissure A much greater degree of similarity existed
waveform
(subject
R.K.)
""T""'T"'"" I"'''r'' T'"'"'T' ""T'"'" T'""'T""" i
F 3 ~,~.//~" 1 ,/~-,-~.,~ ,.,,~
.,, i~/,.r T3
C 5 ~ . :
-J
J
]
11JV
_~..J.........I...... I........J......... I....... l ....... I......... I........ lO 30 50 7 0 ms
Fig 6 Ipsilateral face difference wave form (16-channel montage) and 4 isopotential maps in one subject ( R K )
260
R. KAKIG1, S.J. JONES
Contralateral ''T'T"
difference waveform
palm
(subject K.C.)
.......' " T • ' I T ' I F ' ........' T '
F 7 ~,,_.,...-..n4
Fa
J f C3
jr\
,,-.,~.,_
f
\ J/
J J
/
T 5 ~ . ~ , , _ . . , ~
/ .......I.........I........ I.........L.,LI ....... 10 30 50
k
I.........I....,... 11 p 70
/
ms
Fig. 7, Contralateral palm difference wave form (16-channel montage) and 4 isopotential maps in one subject (K.C.).
Difference waveform Face T-'T'
"T'T'T'
(average of 12 or 8 subjects) Foot
Forearm
T'
T'-T
'
""r
' T ' T - ' - T " T ' " T' ' T '
T '
",r'
I 'T'T'T'T'-T'T'
U41
D22 U36
', ;
U41
U65 032
D 7
?
? lpV
....... I......... I......... I......... I........ I......... I......... I......... I........
10
30 50 I: I p s i l a t e r a l
....... I ......... 1......... I ......... I ......... I ......... I ......... 1......... I ........
10 7 0 ms C : Contralateral
30
50
70
ms
~....I ......... I......... I......... I......... I......... I......... I......... 1........
10
30
50
70
ms
Fig. 8. Group average difference wave forms at F3, C3 and P3 with tactile stimulation of the face, forearm and foot ipsilateral and contralateral to the stimulated median nerve (12 subjects for ipsilateral and 8 subjects for contralateral).
A D J A C E N T A N D REMOTE I N T E R F E R E N C E EFFECTS ON SEPs
between isopotential maps drawn at latencies of 51-59 msec, corresponding with the second downgoing peak. For all 3 interference conditions the peak was maximal over the parietal cortex, spreading to central and temporal regions. For the contralateral palm condition there appeared to be rather more spread to central and frontal electrodes, but this may have been due to confusion between distinct parietal D56 and frontal D69 components.
(5) Interferencefrom other regions of the body surface The tactile interfering stimulus was applied to the forearm and the foot ipsilateral to the stimulated median nerve in 12 subjects, and to the contralateral forearm, face and foot in 8. The difference wave forms derived at F3, P3 and C3 with ipsilateral and contralateral interfering stimulation are shown in Fig. 8. In comparison with the ipsilateral face effect (already described), tactile stimulation of the contralateral perioral area and lips resulted in similar D27 and D52 components in the difference wave form, although both were less well defined. The intervening and following upgoing deflections were much less apparent with the contralateral interfering stimulus. Stimulation of the ipsilateral forearm resulted in a difference wave form in which frontal U41 and centro-parietal D32 components existed concurrently for much of their duration, the former being followed by a D61 and the latter by a D57 peak. With interference from the contralateral forearm the central and parietal difference wave forms were similar to corresponding ipsilateral difference wave forms, although of smaller amplitude. The upward peak at F3, however, was increased in latency by approximately 10 msec, such that there was less suggestion of a polarity inversion relative to C3 and P3. The ipsilateral foot difference wave form consisted of a triphasic pattern at F3 (D22, U36 and D61) and a W-shape at C3 and P3 (D34 and D58). The pattern was very similar when the interfering stimulus was applied to the contralateral foot. In general there was less disparity between difference wave forms obtained with interfering stimulation of the 3 contralateral regions, than between corresponding ipsilateral interference effects.
261
Discussion In a previous study (Jones and Power 1984) the effect of continuous tactile stimulation of the ipsilateral palm on the median nerve SEP was investigated. By subtraction of the 'interference' wave form from the 'control' SEP, a 'difference' wave form was obtained which was highly consistent between individuals. Following parietal 'P'14 and ' N ' 1 9 and frontal 'P'21 potentials, the 2 major components - - 'P'32 and ' N ' 3 6 - - were distributed over the parietal (contralateral) and frontal cortex respectively. Since there was a great deal of temporal overlap between these components, and the zero potential contour closely followed the line of the central sulcus at latencies from 30 to 40 msec, they were considered to be consistent with the field of a dipolar generator oriented in an antero-posterior direction and situated in the region of the central sulcus. The most likely location was thought to be area 3b, which lies in the posterior wall of the central sulcus and is highly responsive to cutaneous stimuli (Powell and Mountcastle 1959). The probable mechanism was considered to be partial 'saturation' of a cortical area concerned with the processing of input from cutaneous mechanoreceptors, such that it was unable to respond fully to the coherent volley evoked by the median nerve impulse. For that reason the difference (control-interference) components were labeled ' P ' and ' N ' according to the usual convention. In the present study, however, it was felt that the assumption that all components were attenuated under all conditions of the interfering stimulus could not be justified, and so the difference potentials were labelled ' U ' and ' D ' without prejudging their true polarity. In the ipsilateral thumb difference wave form, the apparent phase reversals exhibited between D21 and U21, and U34 and D31, were each consistent with the field of a dipolar generator, oriented in an antero-posterior direction and located in the vicinity of the central sulcus. From the nature of the interfering stimulus it can be assumed that this generator was concerned with the processing of input from cutaneous mechanoreceptors in the thumb. The phase reversals seen
262
in the present study, particularly that between D21 and U21, were more nearly complete than those illustrated in the previous paper (Jones and Power 1984), perhaps because a smaller area of cortex was activated. The morphology of the primary cortical evoked response is positive-negative diphasic at the surface and negative-positive at depth (Bartley and Bishop 1933; Li et al. 1956; Mountcastle et al. 1957), so the distribution and polarity of the early components in the thumb difference wave form are consistent with the primary response of a cortical generator situated in the posterior bank of the central sulcus and partially 'saturated' by continuous tactile input. A model based on dipolar cortical generators was proposed by Broughton (dissertation 1967) and elaborated by Allison et al. (1980) to account for the N 2 0 / P 2 0 and P 3 0 / N 3 0 components of the conventional human SEP, although the phase reversals are not clearly seen in the majority of subjects. In primates the primary sensory cortex (SI) can now be subdivided into 4 regions, corresponding to cortical areas 1, 2, 3a and b (see Kaas et al. 1981). Area 3a has been shown to be a receiving area for muscle spindle afferents (Phillips et al. 1971) and is therefore assumed to be concerned with the processing of proprioceptive information. Area 2 was found to be responsive to stimulation of 'deep' (non-cutaneous) bodily tissues (Powell and Mountcastle 1959; Paul et al. 1972), and therefore is also likely to be mainly concerned with proprioception. Units in areas 1 and 3b, however, respond mainly to cutaneous stimuli (Powell and Mountcastle 1959; Paul et al. 1972; Werner and Whitsel 1973; Kaas et al. 1981). In higher primates area 3b is situated on the posterior bank of the central sulcus, whereas area 1 is largely on the crown of the postcentral gyrus (Fig. 9). The most likely generator of the D 2 1 / U 3 4 and U 2 1 / D 3 1 components of the thumb difference wave form, therefore, was considered to be area 3b. In the little finger difference wave form, U32 at the F3 electrode and D31 at P3 were similar to potentials present in the thumb difference wave form (Figs. 2 and 3) and the zero potential contour at this latency approximately followed the line of the central sulcus (Fig. 5). It seems reasonable to propose, therefore, that the early components of
R, KAKIGI, S.J. JONES
the little finger difference wave form might reflect an attenuation of potentials generated in area 3b, as for corresponding peaks in the thumb difference wave form. This may be analogous to the phenomenon of 'surround inhibition' described by Mountcastle and Powell (1959) with regard to single unit responses in the sensory cortex of the monkey. In the present study, however, it was observed that the SEP might be modified by continuous tactile stimulation of the ipsilateral face and foot and regions of the contralateral body surface also, suggesting that there may be an influence from all areas of the skin on cortical elements responding to median nerve input. The distribution of early components in the difference wave form was considerably different for the face and the contralateral palm as compared with the ipsilateral thumb and little finger, suggesting that the interaction may take place in different areas of cortex. in the ipsilateral face difference wave form the D27 potential was widely distributed over frontal, parietal and central regions, being maximal just anterior to the P3 electrode with no evidence of phase reversal. In the contralateral palm d~fference wave form there was also no evidence of phase reversal, but the D27 potential had a more frontal distribution and was not recorded over the temporal cortex below a line approximately overlying the sylvian fissure. The facial region of area 3b is situated on the posterior bank of the inferior part of the central sulcus and is adjacent to the second sensory area, SII. In primates the facial region of the latter is located on the crown of the superior bank of the sylvian fissure (Whitsel et al. 1969; see Fig. 9). Therefore, the distribution of D27 in the face difference wave form was more consistent with a generator in the facial region of SI or SI1 than with the hand region of area 3b. In the contralateral palm difference wave form, the distribution of D27 was perhaps most consistent with a generator in the hand area of SII, which in primates is situated in the superior bank of the sylvian fissure (Whitsel et al. 1969; Fig. 9). The dipolar elements of such a generator would be oriented towards the frontal cortex (where D27 was maximal) and the inferior temporal lobe. Since no phase reversal phenomena were apparent be-
A D J A C E N T A N D R E M O T E I N T E R F E R E N C E EFFECTS ON SEPs
sulcus~..___
Central
~!~n
..
...... ~g
~ *
'.. S1(3,2,1)."Syl vian~,K'~]rA_r~:| ~'~I fissure~~ .............~Tempor lobe
Fig. 9. Schematic representat=on of sensory cortical areas in m a n (after Foerster 1936), showing probable location of SI (arranged from Kaas et al. 1981), SII (arranged from Whitsel et al. 1969) and parietal association areas.
tween precentral and infero-temporal electrodes, however, a generator in precentral cortex adjacent to the site at which D27 was of maximal amplitude is another possibility which cannot be excluded. Neurons in SII differ from those in SI in that their receptive fields are larger, encompassing ipsilateral as well as contralateral areas of the body surface for 63% of units studied in unanesthetized cats (Robinson 1973) and 90% of units in unanesthetized monkeys (Whitsel et al. 1969). Neurons in SII are also particularly responsive to light touch stimulation: Whitsel et al. (1969) reported that 87% of neurons in the SII area of unanesthetized monkeys were activated by cutaneous light touch stimulation. Jones and Powell (1969, 1970), reviewing previous papers, suggested that SII might be an area for interhemispheric convergence of sensory input of all somatic modalities at a relatively low level of cortical function. Although previous reports contain no description of units with receptive fields encompassing such widely separated regions as the hand and the face, their conclusions are broadly compatible with the findings of the present study. The potentials of latency longer than 50 msec were similar for each difference wave form (principally the little finger, face and contralateral palm) except the ipsilateral thumb. The isopotential maps
263
of the second downward potential, D54 for the little finger, D52 for the face and D55 for the contralateral palm, showed very similar distributions, with maxima in the parietal region just anterior to P3 and spreading to all sites in the 16-channel montage but with smaller amplitude in frontal and temporal regions (Figs. 4 and 5). A likely generator for these potentials would be the parietal 'association' cortex, areas 5 a n d / o r 7 (nomenclature of Vogt and Vogt, see Foerster 1936). Although the detailed (16-channel) topographic study was not performed for the thumb, U65 in the difference wave form appeared to be of similar distribution to D54, D52 and D55 in the ipsilateral little finger, face and contralateral pahn difference wave forms, respectively. U65 also, therefore, might be generated in areas 5 a n d / o r 7. Examination and comparison of 'control' and 'interference' wave forms suggests that, whereas U65 may reflect a negative-going component which is attenuated in the thumb interference wave form (see Fig. 2), D54, D52 and D56 may conversely be due to enhancement of a slightly earlier negativity when the interfering stimulus is applied to regions of the body surface outside the sensory distribution of the median nerve (see Fig. 3B). In conclusion, the interference technique has been used to demonstrate interaction between sensory inputs from various parts of the body, manifested in the responses of 'primary' (SI and SII) and 'association' cortical areas. Whereas animal work has done much to elucidate the analytical processes involved with sensation, the SEP technique may prove a more appropriate tool for studying integrative mechanisms which are of equal importance in the context of relating various parts of the body to one another
Resume
Effets sur les P E S du nerf mbdian de stimulations tactiles appliqukes gt des aires adjacentes ou bloignkes de la surface du corps
L'6tude de l'influence de stimulations tactiles continues sur les potentiels 6voqu6s somatosensoriels (PES) produits par la stimulation 61ectrique
264
du nerf m6dian r6v61e un effet dfa h des interf6rences en provenance de r6gions adjacentes et 61oign6es de la surface du corps. La distribution de cet effect a 6t6 6valu6 en soustrayant la r6ponse avec 'interf6rence' de la r6ponse 't6moin' pour obtenir une forme d'onde de 'diff6rence'. La stimulation tactile du pouce ipsilat6ral h la stimulation du nerf m6dian produisait une onde de diff6rence dans laquelle un net renversement de phase 6tait apparent entre les aires pr6- et postcentrale pour 2 complexes, aux latences approximatives de 20 et 30 msec. Peut Etre 6tait-ce dfa /~ une saturation partielle d'un g6n6rateur dans la r6gion de la main de l'aire 3b du cortex somatosensoriel (SI), lequel 6tait alors incapable de r6pondre enti6rement aux influx du nerf m6dian. Un effect similaire a 6t6 observ6 lorsque le stimulus interf6rant 6tait appliqu6 h l'auriculaire ipsilat6ral, refl6tant probablement un processus d'inhibition lat6rale. La stimulation tactile de r6gions plus 61oign6es (principalement de la figure et de la main contralat6rale) fournit des coubes de diff6rence nettes dans lesquelles des composantes pr6coces (latence inf6rieure a 30 msec) ont des distributions de scalp diff6rentes les unes des autres mais en accord avec une influence sur des g6n6rateurs dans la r6gion de la face ou de la main du cortex somatosensoriel secondaire (SII). Des potentiels tardifs bien identifiables dans les courbes de diff6rence 6taient similaires quelle que soit la localisation du stimulus interf6rent sauf le pouce ipsilat6ral et 6talent distribu6s en conformit6 avec l'hypoth6se d'un g6n6rateur dans le cortex associatif pari6tal. We are grateful to Dr. A.M. Halliday for his advice and criticism of the manuscript.
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